Five targets for prospective pharmaceuticals to treat AIDS have been chosen. These are the gp120-CD4 interaction, and the virally-encoded intracellular proteins tat, sor and 3'-orf. In addition, the T cell specific tyrosine kinase lck and its association with CD4 will also be investigated for its suitability as a target. Aspects of the biology and chemistry of these targets will be studied which will facilitate the establishment of assays for the discovery and further examination of lead non-peptidergic and peptide compounds. A large scale screening program will be passed to discover such compounds. In parallel, structural and biophysical studies of domains of the target molecules, and promising lead compounds will be pursued using functional domains developed with properties suitable for NMR and/or x-ray crystallographic analysis. These studies, together with computer modelling, will provide insights and design criteria for the further development of the lead compounds.